Hygrothermal models are important tools for assessing durability risks in building envelopes, such as biological growth (mould and wood rot fungi), corrosion and freeze-thaw action in masonry. Hygrothermal modelling of mass masonry wall assemblies are known to have numerous weaknesses and gaps in our understanding. These include uncertainties relating to model inputs, calibration against data measured in the field, poorly understood two and three-dimensional interactions between adjacent materials, and the effect of geometric irregularities, imperfections and decay. Combined, these uncertainties can lead to reduced confidence in the model's conclusion and alter our opinions on the durability risks and whether certain retrofits are appropriate or not. This integrated doctoral thesis examines how uncertainty factors into hygrothermal as demonstrated using a combination of simulation studies and on-site monitoring work. First, a methodology for integrating calibrated hygrothermal and energy models of the Southwest Tower of the East Block for the purpose of assessing durability is demonstrated. This project consisted of in-situ monitoring of the masonry and interior climate of the tower for over a year. The calibrated energy model was used as basis for estimating the net benefit of interior climate retrofits on the durability of the masonry. Second, the imperfect nature of the mortar-unit interface in masonry and how this affects moisture transfer into and out of the wall is examined. Simulations showed that modelling this interface explicitly as a fracture will increase water absorption during wetting periods, but also help slightly with releasing moisture under drying conditions. And third, the uncertainty in geometry and construction of the rubble core walls is examined. The examined walls have highly irregular geometry and are known to have significant voids. A Python script was developed to stochastically generate sections of walls with and without voids. A significant variation in state variables, and heat and moisture fluxes was found between stochastically generated geometries and this variation increased with the number of voids. Overall, this research contributes to efforts make hygrothermal modelling of masonry more accurate and intuitive and how establishing sound baseline models and uncertainty windows is key to confidently estimating the deterioration risk in masonry.